IMPORTANCE DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. OBJECTIVE To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). DESIGN, SETTING, AND PARTICIPANTSThe VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020.INTERVENTIONS Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses). MAIN OUTCOMES AND MEASURESThe primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status. RESULTS A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21; P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]). CONCLUSIONS AND RELEVANCEIn this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated.

PURPOSE Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641 ) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR−, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR− cohort. RESULTS Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR− cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events. CONCLUSION Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

Study design: This was a multicentre, prospective, randomised study. Objectives: To compare the outcomes of intradetrusor and suburothelial onabotulinumtoxinA injections in patients with spinal cord injury and refractory neurogenic detrusor overactivity (NDO). Setting: Urology departments of two tertiary hospitals in the Czech Republic. Methods: A total of 32 spinal cord injury patients with severe NDO refractory to the standard anticholinergic treatment were randomised to receive either intradetrusor or suburothelial 300 IU onabotulinumtoxinA injections. Subjective satisfaction, bladder diary data and urodynamic data were compared in both groups before treatment and at 3 months post treatment. Results: In all, 64.3% patients in the intradetrusor group and 88.8% patients in the suburothelial group were subjectively satisfied with the treatment. There was a significant post-treatment improvement in both groups regarding the number of catheterisations over 24 h, number of incontinence episodes over 24 h, catheterised volume, cystometric capacity, volume at first involuntary detrusor contraction, maximal detrusor pressure during filling and detrusor compliance. No significant differences between the groups were observed, with the exception of improvement of detrusor compliance, which was better in the intradetrusor group. There was one adverse effect comprising transient muscle weakness that was reported by one patient in the intradetrusor group. Conclusion: Results in both groups were comparable. The authors favour suburothelial onabotulinumtoxinA injection because this method allows more precise toxin localisation. Spinal Cord (2012) 50, 904-907; doi:10.1038/sc.2012.76; published online 17 July 2012Keywords: urodynamics; neurogenic detrusor overactivity; onabotulinumtoxinA; spinal cord injury; suburothelial injection INTRODUCTION Spinal cord injuries are among the most devastating of all injuries, often having life-changing and diverse consequences. Lower urinary tract dysfunction is commonly observed as a result of a spinal cord injury. Neurogenic detrusor overactivity (NDO) is frequently associated with upper motor neuron lesion, and the subsequent increased intravesical pressure may present a potential risk by causing damage to the upper urinary tract. 1 Current standard NDO treatment comprises individualised administration of anticholinergic medication; however, this therapy is inadequate for some patients and is often associated with unacceptable adverse effects. 2 Treatment with botulinum toxin offers an accepted alternative treatment for those patients in whom anticholinergic treatment has failed.Botulinum toxin is a neurotoxin produced by anaerobic microorganisms of the Clostridium genus. Botulinum toxin acts on the peripheral nervous system where it is responsible for blockade of acetylcholine release from presynaptic nerve endings. 3 This process results in blockade of the neuromuscular transfer, with a subsequent loss of muscle cell contractility.A further effect of botulinum toxin following administra...

Introduction: Apart from the standard intramural administration of botulinum neurotoxin A (BoNT/A) to the detrusor, intense research is taking place into new means of administration in view of the complex mechanism of action of BoNT/A. Methods: An open, randomised, prospective study was performed on a total of 23 patients with neurogenic detrusor overactivity. Following randomisation, patients were treated with 300 U of onabotulinumtoxinA (onaBoNT/A) in either the submucosa or the detrusor. Urodynamic examinations were carried out, and a bladder diary was kept both prior to and 12 weeks after the treatment. All patients stopped taking anticholinergics 1 week prior to the treatment. Results: In both the submucosa and detrusor groups, we recorded a significant improvement in the monitored urodynamic parameters and significant decreases in the frequency of urinary incontinence episodes following the treatment. A comparison of the two groups showed no significant difference between the two forms of application, with the exception of voided volume (p = 0.007). Conclusion: A comparison of the two administration methods did not show any significant difference between onaBoNT/A administration to the submucosa and to the detrusor. Thus, the submucosal injection of onaBoNT/A represents an equally effective approach for its administration to patients.